Enhanced survival of BCG-stimulated dendritic cells: involvement of anti-apoptotic proteins and NF-κB

Biology Open
Pawan KumarSangeeta Bhaskar

Abstract

BCG (Bacillus Calmette-Guérin) is the only available vaccine against TB and is also used for the treatment of superficial bladder cancer. BCG-mediated protection against TB and bladder cancer has been shown to rely on its ability to induce superior CD4+ and CD8+ T cell responses. As the magnitude of T cell responses is defined by dendritic cell (DC) lifespan, we examined the effect of BCG on DC survival and its underlying mechanisms. It was observed that BCG stimulation enhanced DC survival and prolonged DC lifespan in a dose-dependent manner. Live BCG led to a higher DC survival compared with heat-killed BCG. FITC-Annexin V staining showed that BCG promoted DC survival by inhibiting apoptosis. Consistently, higher expressions of anti-apoptotic proteins Bcl-2 and Bcl-xL were observed in BCG-stimulated DCs. Pharmacological inhibition of Bcl-2 and Bcl-xL drastically reduced the DC survival efficacy of BCG. Comparable survival of BCG-stimulated wild-type and MyD88-/- DCs suggested that MyD88 signaling is dispensable for BCG-induced DC survival. NF-κB is one of the key regulators of innate immune responses. We observed that pharmacological inhibition of NF-κB abrogated BCG-mediated increase in DC survival and expression of anti-apo...Continue Reading

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Citations

May 3, 2020·Anti-cancer Agents in Medicinal Chemistry·Yang LuoMinjie Meng

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
flow cytometry
protein assay

Software Mentioned

GraphPad Prism

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